Study suggests new treatment approach needed for management of depression with bipolar disorder

ROCHESTER, Minn. -- In a study published in The American Journal of Psychiatry, a team of researchers led by Mayo Clinic psychiatrist Mark Frye, M.D., attempted to identify what factors make some people with bipolar depression more likely to experience treatment-emergent mania (TEM).

Bipolar disorder, also known as manic-depressive illness, is a mental illness characterized by severe mood instability that can be serious and disabling. The deep mood swings from high (mania) to low (depression) may last for weeks or months, causing great disturbances in the lives of the person who has the illness, along with family and friends. Drugs known as mood stabilizers have proven effective at controlling the manic phase of the illness, but treating the depressive phase is more problematic. Antidepressants, although effective for some individuals, can trigger a rapid mood switch from depression to mania, a phenomenon called treatment-emergent mania.

"TEM is a serious and sometimes volatile adverse event, and we wanted to better understand who was at risk for developing this problem," says Dr. Frye. People experiencing mania often exhibit poor judgment and impulsivity that can lead them to engage in highly unsafe or personally damaging behaviors, resulting in hospitalization, arrest and/or incarceration.

Dr. Frye's team did a secondary analysis of data obtained in an earlier study led by Robert Post, M.D., and the Bipolar Collaborative Network. In that earlier study, researchers followed 176 study participants diagnosed with bipolar depression to measure the effectiveness of three different antidepressants. The secondary analysis led by Dr. Frye focused on 44 patients who experienced TEM after starting an antidepressant. Dr. Frye's team compared this TEM group to 84 patients who responded favorably to an antidepressant and 44 patients who stopped taking the antidepressant due to lack of effectiveness or worsening depressive symptoms.

"We found that people who had minimal manic symptoms or a "mixed depression" presentation were at greatest risk for experiencing TEM," says Dr. Frye.

Experts have begun to acknowledge that the common understanding of bipolar illness, once thought to be a disorder with two distinct phases (a manic upswing and a depressive downswing), may be incomplete. A recent study of over 1,300 patients conducted by Joseph Goldberg, M.D., Mount Sinai School of Medicine, reported that two-thirds of the depressed bipolar patients had minimal or mild manic symptoms "mixed" together.

"We're learning that this illness does not occur in two neat, clear-cut phases, but rather a mix of the two," says Dr. Frye. "Our data would suggest that people with mixed depression may need to stay away from antidepressants and work with their health care providers to find alternative treatments, such as mood stabilizers, to help manage the depressive phase of their illness." Further research is encouraged to better understand the best treatment for these mixed presentations.

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Other authors for this article include: Gerhard Helleman, Ph.D., David Geffen School of Medicine at UCLA, Los Angeles; Susan McElroy, M.D., University of Cincinnati College of Medicine; Lori Altshuler, M.D., David Geffen School of Medicine at UCLA, Los Angeles; David Black, Ph.D., Pediatric and Developmental Neuropsychiatry, National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, Md., and David Geffen School of Medicine at UCLA, Los Angeles; Paul Keck Jr., M.D., University of Cincinnati College of Medicine; Willem Nolen, M.D., Ph.D., University Medical Center Groningen, University of Groningen, the Netherlands; Ralph Kupka, M.D., Ph.D., Altrecht Institute for Mental Health Care and University Medical Centre, Utrecht, the Netherlands; Gabriele Leverich, Biological Psychiatry Branch, NIMH, NIH, Bethesda, Md.; Heinz Grune, M.D., Institute of Neuroscience, Newcastle University, Newcastle, England; Jim Mintz, Ph.D., University of Texas San Antonio; Robert Post, M.D., George Washington School of Medicine, Penn State College School of Medicine and Bipolar Collaborative Network, Bethesda, Md.; and Trisha Suppes, M.D., Ph.D., Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas.

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